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AbbVie Organic Seminar – Dr. Russ Cink, AbbVie

March 1 @ 11:00 am - 12:00 pm

Event Presenter:

Dr. Russ Cink

Institution:

AbbVie

Categories:

Organic, AbbVie Seminar, Special Seminar

PROCESS DEVELOPMENT OF GLECAPREVIR

Man in blue shirt smiling

Glecaprevir was identified as a potent hepatitis C virus (HCV) protease inhibitor, and an enabling synthesis was required to support the preclinical evaluation and subsequent Phase I clinical trials. The key steps in the enabling route involved a ring-closing metathesis (RCM) reaction to form the 18-membered macrocycle and a challenging fluorination step to form a key difluoromethyl-substituted cyclopropyl amino acid. To support the late-stage clinical trials and subsequent commercial launch, a large-scale synthetic route to glecaprevir was required. The large-scale synthetic route to the macrocycle employed a unique intramolecular etherification reaction as the key step, avoiding the scalability limitations of the ring-closing metathesis (RCM) reaction of the enabling route. The large-scale route to the difluoromethyl-substituted cyclopropyl amino acid avoided the fluorination challenges by constructing the amino acid from a commercially available difluoromethyl-substituted hemi-acetal.  The key steps in the amino acid synthesis were a Knoevenagel condensation, a Corey-Chaykovsky cyclopropanation, a Curtius rearrangement, and a chiral resolution.  Subsequent coupling of the macrocycle to the amino acid containing sidechain produced glecaprevir in 16% overall yield.

AbbVie Seminar Poster

FOR MORE INFORMATION. PLEASE CONTACT: MARY HANDSON AT MCHANSO1@WISC.EDU OR

ALISA GRADNEY AT AGRADNEY@WISC.EDU

Details

Date:
March 1
Time:
11:00 am - 12:00 pm
Event Categories:
, ,

Venue

2120 Grainger Hall
975 University Avenue
Madison, 53706 United States